Background

Ileus occurs from hypomotility of the gastrointestinal tract in the absence of mechanical bowel obstruction. Although the exact pathogenesis of ileus remains multifactorial and complex, the clinical picture appears to be transiently impaired propulsion of intestinal contents. The complex interaction between autonomic and central nervous system function, as well as local and regional substances, may alter the intestinal equilibrium, resulting in disorganized electrical activity and paralysis of intestinal segments. This lack of coordinated propulsive action leads to the accumulation of gas and fluids within the bowel.

Note the images below.

View Image

Postoperative ileus after an open cholecystectomy.

View Image

Ogilvie pseudo-obstruction in a septic elderly patient. Note the massive dilatation of the colon, especially the right colon and cecum.

Although ileus has numerous causes, the postoperative state is the most common setting for the development of ileus. Indeed, ileus is an expected consequence of abdominal surgery. Physiologic ileus spontaneously resolves within 2-3 days, after sigmoid motility returns to normal. Ileus that persists for more than 3 days following surgery is termed postoperative adynamic ileus or paralytic ileus.[1] Frequently, ileus occurs after major abdominal operations, but it may also occur after retroperitoneal and extra-abdominal surgery, as well as general anesthesia alone. The longest duration of ileus is noted to occur after colon and rectal surgery.[2, 3] Laparoscopic colon resection has been associated with shorter periods of ileus than open colon and rectal resection.[4]

The clinical consequences of postoperative ileus can be profound. Patients with ileus are immobilized, have discomfort and pain, and are at increased risk for pulmonary complications. Ileus also enhances catabolism because of poor nutrition. Overall, ileus increases the cost of medical care because it prolongs hospital stays. In 1990, Livingston and Passaro estimated that ileus costs $750 million annually ($1500 per patient) in the United States.[1]

The investigators found the presence of postoperative ileus was found to be a significant predictor of hospitalization costs (P < .001), controlling for covariates.[5] The authors concluded that postoperative ileus in colectomy patients is a significant predictor of hospital resource utilization.

Pathophysiology

The exact pathogenesis of ileus remains unclear. Postoperative ileus may be mediated via activation of inhibitory spinal reflex arcs. Anatomically, 3 distinct reflexes are involved: ultrashort reflexes confined to the bowel wall, short reflexes involving prevertebral ganglia, and long reflexes involving the spinal cord.[3] The long reflexes are the most significant. Spinal anesthesia, abdominal sympathectomy, and nerve-cutting techniques have been demonstrated to either prevent or attenuate the development of ileus.[6, 7]

The surgical stress response leads to systemic generation of endocrine and inflammatory mediators that also promote the development of ileus. Rat models have shown that laparotomy, eventration, and bowel compression lead to increased numbers of macrophages, monocytes, dendritic cells, T cells, natural killer cells, and mast cells, as demonstrated by immunohistochemistry.[8] Macrophages residing in the muscularisexterna and mast cells are probably the key players in this inflammatory cascade.[9] Calcitonin gene–related peptide, nitric oxide, vasoactive intestinal peptide, and substance P function as inhibitory neurotransmitters in the bowel nervous system. Nitric oxide and vasoactive intestinal peptide inhibitors and substance P receptor antagonists have been demonstrated to improve gastrointestinal function.[10, 11]

Epidemiology

Frequency

United States

Postoperative ileus occurs in approximately 50% of patients who undergo major abdominal surgery.[12] Kuruba et al studied the incidence and risk factors for prolonged ileus in patients undergoing elective colon surgery retrospectively. The incidence of prolonged ileus was similar in patients with epidural versus nonepidural versus laparoscopic surgery. The incidence of prolonged ileus was similar in all 3 groups studied.[13]

A pooled, post-hoc, phase III study analyzed placebo groups and partial bowel resection and total abdominal hysterectomy multicenter trials.[14] Postoperative ileus was still observed in 15% of patients in the partial bowel resection group and in 3% of the total abdominal hysterectomy patients, regardless of the standardized accelerated postoperative care pathway used. This study also provides significant differences in gastrointestinal recovery patterns between bowel resection and total abdominal hysterectomy.

History

Patients with ileus typically have vague, mild abdominal pain and bloating. They may report nausea, vomiting, and poor appetite. Abdominal cramping is usually not present. Patients may or may not continue to pass flatus and stool.

Physical

The abdomen may be distended and tympanic, depending on the degree of abdominal and bowel distention, and may be tender. A distinguishing feature is absent or hypoactive bowel sounds, in contrast to the high-pitched sound of obstruction. The silent abdomen of ileus reveals no discernible peristalsis or succussion splash.

Causes

Most cases of ileus occur after intra-abdominal operations. Normal resumption of bowel activity after abdominal surgery follows a predictable pattern: the small bowel typically regains function within hours; the stomach regains activity in 1-2 days; and the colon regains activity in 3-5 days.[15]

Serial abdominal radiographs mapping the distribution of radiopaque markers have shown that the colonic gradient for resolution of postoperative ileus is proximal to distal. The return of propulsive activity to the right colon occurs earlier than to the transverse or left colon.[16]

Imaging Studies

On plain abdominal radiographs, ileus appears as copious gas dilatation of the small intestine and colon. With enteroclysis, the contrast medium in patients with paralytic ileus should reach the cecum within 4 hours; if the contrast medium remains stationary for longer than 4 hours, mechanical obstruction is suggested.[19]

Medical Care

The management of ileus may vary greatly depending on the nature of the disease and the surgical procedure. Management of ileus starts with correction of underlying medical conditions, electrolyte abnormalities, and acid base abnormalities.

Most cases of postoperative ileus resolve with watchful waiting and supportive treatment. Patients should receive intravenous hydration. For patients with vomiting and distention, use of a nasogastric tube provides symptomatic relief; however, no studies in the literature support the use of nasogastric tubes to facilitate resolution of ileus. Long intestinal tubes have no benefit over nasogastric tubes.

For patients with protracted ileus, mechanical obstruction must be excluded with contrast studies. Underlying sepsis and electrolyte abnormalities, particularly hypokalemia, hyponatremia, and hypomagnesemia, may worsen ileus. These contributing conditions are easily diagnosed and corrected.

Discontinue medications that produce ileus (eg, opiates). In one study, the amount of morphine administered directly correlated with the time elapsed before the return of bowel sounds and the passage of flatus and stool.[20]

The use of postoperative narcotics can be diminished by supplementation with nonsteroidal anti-inflammatory drugs (NSAIDs). In addition to permitting lower narcotic doses by providing pain relief, NSAIDS may improve ileus by reducing local inflammation. Myoelectric activities recorded from electrodes placed on the colon have revealed faster resolution from ileus in patients given ketorolac versus those given morphine[21] ; however, the drawbacks of NSAID use include platelet dysfunction and gastric mucosal ulceration. Consider the use of a cyclooxygenase-2 selective agent (ie, celecoxib), which negates these adverse effects.

No single objective variable accurately predicts the resolution of ileus. The clinician must assess the overall status of the patient and evaluate for adequate oral intake and good bowel function. A patient's report of flatus, bowel sounds, or stool passage may prove misleading; therefore, clinicians must not rely solely on self-reporting.

Diet

It is generally advisable to delay oral feeding until ileus resolves clinically. However, the presence of ileus does not preclude enteral feeding. Postpyloric feeding into the small bowel can be cautiously performed. Start feeds at one-quarter or one-half strength at a slow rate and gradually advance.

Having patients chew gum has been advocated as a means of promoting recovery from postoperative ileus. Chewing gum may constitute a form of sham feeding that stimulates gastrointestinal motility. Meta-analyses have shown that gum chewing can reduce the time to first flatus and passage of feces, and marginally decrease the length of hospital stay after intestinal surgery.[4, 22, 23]

Activity

Conventional wisdom and wide practice foster the notion that ambulation stimulates bowel function and improves postoperative ileus, although this has not been shown in the literature.

In a nonrandomized study evaluating 34 patients, seromuscular bipolar electrodes were placed in segments of the gastrointestinal tract after laparotomy. Ten patients were assigned to ambulate on postoperative day 1, and the other 24 were assigned to ambulate on postoperative day 4. No significant difference between the 2 groups was displayed in myoelectric recovery in the stomach, jejunum, or colon.[24] Hence, postoperative ambulation remains beneficial in preventing the formation of atelectasis, deep vein thrombosis, and pneumonia but has no role in treating ileus.

Medication Summary

Thoracic epidural administration has been shown to be beneficial, both with open and with endoscopic colorectal surgery.[25] Epidural blockade with local anesthetics improves postoperative ileus by blockage of inhibitory reflexes and efferent sympathetics. Studies have shown that combinations of thoracic epidurals containing bupivacaine alone or in combination with opioids improve postoperative ileus.[26, 27] Continuous intravenous administration of lidocaine during and after abdominal surgery may decrease the duration of postoperative ileus.[28]

In a randomized study, systemic infusion of lidocaine is compared with placebo infusions in postoperative patients. Patients in the lidocaine group appear to have earlier return of flatus, bowel function, and discharge to home. Although only 11 patients were used in the each arm, systemic lidocaine lessened the postoperative pain sensation. Therefore, it is recommended that further studies are warranted to evaluate systemic lidocaine infusion in postoperative patients.[29]

Peripherally selective opioid antagonists are an option for the treatment of postoperative ileus.[30] Methylnaltrexone (Relistor) and alvimopan (Entereg) are approved by the Food and Drug Administration. These agents inhibit peripheral mu-opioid receptors, which abolishes the adverse gastrointestinal effects of opioids; however, because these agents do not cross the blood-brain barrier, they do not impair the analgesic effects of opioids.[31] Methylnaltrexone is indicated for opioid-induced constipation in patients with advanced illness receiving palliative care, when response to laxatives has not been sufficient. In a study of 14 healthy volunteers evaluating the use of morphine plus oral methylnaltrexone in increasing doses, methylnaltrexone significantly reduced morphine-induced delay in oral-cecal transit.[32] Another study reported subcutaneous methylnaltrexone is effective in inducing laxation in patients receiving palliative care who have opioid-induced constipation and inwhomconventionallaxatives have failed.[33] However, because methylnaltrexone has only recently been approved by the US Food and Drug Administration (FDA), more rigorous trials are needed.

Another phase III multicenter, double-blind, placebo-controlled study revealed that methylnaltrexone at 12-mg and 24-mg doses did not reduce the duration of postoperative ileus.[34] Although the utility of intravenous methylnaltrexone was not demonstrated, it was well tolerated by postcolectomy patients.[34]

Alvimopan is indicated to help prevent postoperative ileus following bowel resection. It has a longer duration of action than methylnaltrexone. Taguchi et al examined 78 postoperative patients randomized to receive either placebo or alvimopan.[35] Fifteen patients underwent partial colectomy, 36 were status post simple hysterectomy, and the remaining 27 underwent radical hysterectomy. All of the patients were on patient-controlled analgesia pumps using either meperidine or morphine. Compared with patients on placebo, patients on alvimopan had their first bowel movement 2 days earlier, resumed a solid diet 1.3 days earlier, and returned home 1.4 days earlier. Other recent trials have been completed, including a meta-analysis comparing alvimopan with placebo[36] and a study that found alvimopan to accelerate gastrointestinal tract recovery after bowel resection, regardless of age, gender, race, or concomitant medication.[37]

Use of prokinetic agents has shown mixed results. Randomized trials have shown some benefit of the colon-stimulating laxative bisacodyl for the treatment of ileus.[38, 39] Erythromycin, a motilin receptor agonist, has been used for postoperative gastric paresis but has not been shown to be beneficial for ileus.[40] Metoclopramide (Reglan), a dopaminergic antagonist, has antiemetic and prokinetic activities, but data have shown that the drug may actually worsen ileus. In a randomized controlled study on 210 patients undergoing major abdominal surgery, Wattchow et al reported that perioperative low dose celecoxib markedly reduced the development of paralytic ileus compared to diclofenac.[41] The effect was independent of narcotic use and was not associated with any increase in postoperative complications.

A review of meta-analyses and randomized controlled trials on drugs used for post-operative ileus was reported by Yeh et al.[42] The investigators identified three meta-analyses (2 on gum-chewing and 1 on alvimopan) and 18 clinical trials. Only gum chewing and alvimopan were effective in preventing ileus but due to safety concerns and costs with alvimopan, gum chewing may be preferred as first-line therapy. Gum chewing has also been used in women recovering from cesearian section with good effect when compared to standard of care in a randomized study conducted.[43]

Only available to hospitals after they complete a registration process designed to maintain the benefits associated with short-term use and prevent long-term, outpatient use (Entereg Access Support and Education [EASE] program).